Pharmacotherapy in a Multidisciplinary Paediatric Hospital: Polypharmacy and Drug–Drug Interaction Risk Illustrated with a Clinical Case

Nowadays, the problems caused by polypharmacy are recognised and widely discussed in the medical community. Multimorbidity, which is not uncommon in paediatric practice, comes with an increase in the number of prescriptions and necessitates an active search for tools to reduce the potential risk and frequency of adverse drug–drug interactions in paediatric patients.The aim of the study was to use a clinical case to illustrate the need for monitoring, including laboratory monitoring of pharmacokinetic parameters, during concomitant therapy in paediatric practice.Materials and methods: the study consisted in a retrospective analysis of the archived medical records of an 11-year-old child with nephrotic syndrome associated with a concomitant tuberculous process who had been receiving inpatient treatment with immunosuppressants at the Russian Children’s Clinical Hospital from May to July 2018.Results: the prescription of cyclosporine for nephrotic syndrome entailed monitoring of plasma drug levels for potential pharmacokinetic interactions with the medicinal products used to treat the concomitant disease. The monitoring revealed an interaction between cyclosporine and rifampicin at the level of biotransformation. An adjustment of the concomitant therapy (discontinuation of rifampicin) allowed for achieving the target blood cyclosporine concentration, decreasing proteinuria and hypercholesterolemia, and increasing the blood total protein level in the child, which indicated the effectiveness of the ongoing treatment for the chief complaint.Conclusions: the data obtained suggest that laboratory monitoring of pharmacokinetic parameters in paediatric polypharmacy can increase the effectiveness of therapy and prevent adverse reactions and irrational combination of medicinal products

Stationary Distribution and Eigenvalues for a de Bruijn Process

We define a de Bruijn process with parameters n and L as a certain continuous-time Markov chain on the de Bruijn graph with words of length L over an n-letter alphabet as vertices. We determine explicitly its steady state distribution and its characteristic polynomial, which turns out to decompose into linear factors. In addition, we examine the stationary state of two specializations in detail. In the first one, the de Bruijn-Bernoulli process, this is a product measure. In the second one, the Skin-deep de Bruin process, the distribution has constant density but nontrivial correlation functions. The two point correlation function is determined using generating function techniques.Comment: Dedicated to Herb Wilf on the occasion of his 80th birthda

Neurotoxicity of drugs

Neurotoxicity is not uncommon in use of the drugs in many therapeutic classes. Manifestations of neurotoxicity vary from ototoxicity, visceral neuropathy and neuromuscular blockade (defeat of the peripheral nervous system) to impaired consciousness, nonspecific encephalopathy, seizures and non-convulsive epileptic status (central nervous system damage). The article presents predisposing factors of neurotoxicity, as well as the mechanisms of its development. On the example of neuroactive drugs (anticonvulsants, anesthetics and psychotropic drugs) their effect in the antenatal period and during lactation is examined. In the post-neonatal period antibiotics play an important role in the neurotoxic effect, in particular, ß-lactams and fluoroquinolones

Распространенность аллергических заболеваний у подростков

A screening search of 495 adolescents found bronchial asthma in 7.45 % and allergic diseases (AD) in general in 44.8 %. Most frequent AD were allergic rhinitis (16.6 %) and skin lesions (15.1 %). AD patients considerably more often nave respiratory signs (cough, breathlessness, sputum, wheezing), bronchial obstruction (22.7 % vs. 6.6 %, P < 0.05) and bronchial hyperresponsiveness (34.3 % vs. 5.7 %, P < 0.05) as compared to controls.При скрининговом обследовании 495 подростков установлено, что бронхиальная астма у них встречается в 7,45 % случаев, а в целом аллергические заболевания (АЗ) - в 44,8 % случаев. Наиболее частыми среди аллергозов были аллергический ринит (16,6 %) и кожные проявления (15,1 %). У лиц с АЗ, по сравнению с контролем, достоверно чаще наблюдаются все респираторные симптомы (кашель, одышка, мокрота, сухие хрипы в легких), обструкция бронхов (22,7 % против 6,6 %; Р < 0,05) и высокая реактивность бронхов (34,3 % против 5,7 %; Р < 0,05)

Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants

Objective: To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. Methods: We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. Results: We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p 6.4 × 10-28 for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p 2.7 × 10-20 for the CE score in MO). Conclusions: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype